Search

Background & Aims: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting, and data from multicentre studies are scarce. The aim of this study was to dissect the potential association between PPI use and minimal (MHE) and overt HE (OHE). Methods: Data from patients with cirrhosis recruited at seven centres across Europe and the US were analysed. MHE was defined by the psychometric hepatic encephalopathy score (PHES). PPI use was recorded on the day of testing with PHES. Patients were followed for OHE development and death/liver transplantation. Results: A total of 1,160 patients with a median MELD of 11 were included (Child-Pugh stages: A 49%/B 39%/C 11%). PPI use was noted in 58% of patients. Median follow-up time was 18.1 months, during which 230 (20%) developed an OHE episode, and 224 (19%) reached the composite endpoint of death/liver transplantation. In multivariable analyses, PPI use was neither associated with the presence of MHE at baseline nor OHE development during follow-up. These findings were consistent in subgroup analyses of patients with Child-Pugh A or B cirrhosis and after excluding patients with a history of OHE. PPI use was also not associated with a higher risk of OHE, neither in patients with an indication for treatment nor in patients without an indication. Conclusions: PPI use is not associated with a higher risk of HE in patients with cirrhosis. Based on these findings, at present, a prescription should not be prohibited in case of a generally accepted indication. Impact and implications: Data on the association between proton pump inhibitor (PPI) use and hepatic encephalopathy (HE) are conflicting. In this study, PPI use was not associated with a higher risk of minimal HE at baseline or overt HE during follow-up in patients with cirrhosis. Based on these findings, prescription of a PPI for a generally accepted indication should not be prohibited in patients with cirrhosis.

Background: Hepatic encephalopathy (HE) is highly prevalent in patients with liver diseases. The pathophysiology of HE is centered on the synergic role of hyperammonemia and systemic inflammation. However, some data suggest altered functioning of the blood–brain barrier (BBB). Assessing BBB function is challenging in clinical practice and at the bedside. Protein-S-100 Beta (PS100-Beta) could be a useful peripheral marker of BBB permeability in HE. This study aimed to assess plasmatic PS100-Beta levels in a prospective cohort of patients admitted to the intensive care unit (ICU) with decompensated cirrhosis with and without overt HE. Methods: We retrospectively evaluated a prospective cohort of cirrhotic patients admitted to the ICU from October 2013 to September 2015 that had an available plasmatic PS100-Beta measurement. Patients with previous neurological impairment or limitation of intensive or resuscitative measures were excluded. Overt HE was defined as West-Haven grades 2 to 4. The patients were compared to a control cohort of outpatient clinic cirrhotic and non-cirrhotic patients explored for isolated elevation of liver enzymes. After ICU discharge, the patients were followed for at least 3 months for the occurrence of overt HE. Adverse outcomes (liver transplantation or death) were collected. The ability of PS100-Beta – in combination with other factors – to predict overt HE was evaluated in a multivariate analysis using logistic regression. Likelihood ratios were used to determine the effects and calculate odds ratios (OR). Survival analysis was performed by using the Kaplan–Meier method and survival between groups was compared using a Log-rank test. Results: A total of 194 ICU patients and 207 outpatients were included in the study. Increased levels of plasmatic PS100-Beta were detected in the ICU decompensated cirrhotic patients compared with the outpatients ([0.15±0.01] mg/L vs. [0.08±0] mg/L, P